| 1. |
- Woitowich, N. C., et al.
(författare)
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Structural basis for light control of cell development revealed by crystal structures of a myxobacterial phytochrome
- 2018
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Ingår i: Iucrj. - : International Union of Crystallography (IUCr). - 2052-2525. ; 5:Part 5, s. 619-634
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Tidskriftsartikel (refereegranskat)abstract
- Phytochromes are red-light photoreceptors that were first characterized in plants, with homologs in photosynthetic and non-photosynthetic bacteria known as bacteriophytochromes (BphPs). Upon absorption of light, BphPs interconvert between two states denoted Pr and Pfr with distinct absorption spectra in the red and far-red. They have recently been engineered as enzymatic photoswitches for fluorescent-marker applications in non-invasive tissue imaging of mammals. This article presents cryo- and room-temperature crystal structures of the unusual phytochrome from the non-photosynthetic myxobacterium Stigmatella aurantiaca (SaBphP1) and reveals its role in the fruitingbody formation of this photomorphogenic bacterium. SaBphP1 lacks a conserved histidine (His) in the chromophore-binding domain that stabilizes the Pr state in the classical BphPs. Instead it contains a threonine (Thr), a feature that is restricted to several myxobacterial phytochromes and is not evolutionarily understood. SaBphP1 structures of the chromophore binding domain (CBD) and the complete photosensory core module (PCM) in wild-type and Thr-to-His mutant forms reveal details of the molecular mechanism of the Pr/Pfr transition associated with the physiological response of this myxobacterium to red light. Specifically, key structural differences in the CBD and PCM between the wild-type and the Thr-to-His mutant involve essential chromophore contacts with proximal amino acids, and point to how the photosignal is transduced through the rest of the protein, impacting the essential enzymatic activity in the photomorphogenic response of this myxobacterium.
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| 2. |
- Bibikova, E. V., et al.
(författare)
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The early crust of the Volgo-Uralian segment of the East European Craton: Isotope-geochronological zirconology of metasedimentary rocks of the Bolshecheremshanskaya Formation and their Sm-Nd model ages
- 2015
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Ingår i: Stratigraphy and Geological Correlation. - 0869-5938. ; 23:1, s. 1-23
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Tidskriftsartikel (refereegranskat)abstract
- We present the results of isotope-geochronological study of metasedimentary rocks of the Bolshecheremshanskaya Formation of the Volgo-Uralian segment of the East European Craton carried out to identify their protoliths. 16 samples of high-alumina gneisses from well cores were studied using the Sm-Nd isotope method and T-Nd(DM) model ages. Accessory zircons were selected from rocks with the most ancient model ages (more 3.2 Ga) in three wells: Minnibaevskaya 20000, Novo-Elkhovskaya 20009, and Zai-Karatayskaya 12930 in South Tatarstan. The isotope U-Pb dating of 200 zircon grains was performed on a Cameca 1280 NORDSIM secondary ion mass spectrometer at the Natural History Museum (Stockholm, Sweden). The most applicable sites for analysis of zircon crystals were pre-selected based on cathodoluminescence images. The analytical results demonstrate the diversity of zircon groups in age from 3.8 to 2.6 Ga and together with geochemical features of metasedimentary rocks of the Bolshecheremshanskaya Formation suggest the heterogeneous composition and age of provenance areas under denudation. Occurrence of Eoarchean and Paleoarchean zircons in the clastic material of the protolith of the Bolshecheremshanskaya gneisses indicates the existence of Early Archean crustal terrains in Volgo-Uralia.
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| 3. |
- Fedotova, A. A., et al.
(författare)
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New Data on the Paleoproterozoic Age of Metamorphism in the Yelabuga Deformation Zone of Volgo-Uralia, East European Craton
- 2019
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Ingår i: Doklady Earth Sciences. - 1028-334X. ; 488:1, s. 1123-1127
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Tidskriftsartikel (refereegranskat)abstract
- Abstract: This data on the age of metamorphism of rocks of the Yelabuga zone and the geochronological data on detrital zircon from paragneisses of the same zone are presented, and their correlation with the ages of rocks from the Middle Volga megablock is made. The rocks of the Yelabuga zone and Middle Volga megablock have similar geochemical characteristics and degrees of metamorphism, but demonstrate the following differences: Paleoproterozoic metamorphism was clearly expressed in the studied rocks of the Yelabuga zone, which contrasts to rocks of the Middle Volga megablock, where no metamorphism of this age is manifested. The study of the U–Pb isotopic system in external zones of zircon crystals from the Yelabuga deformation zone suggests that rocks underwent two stages of metamorphism, 1.99 and 1.95 Ga ago.
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| 4. |
- Sanchez, J. C., et al.
(författare)
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High-resolution crystal structures of amyxobacterial phytochrome at cryo and roomtemperatures
- 2019
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Ingår i: Structural Dynamics-Us. - : AIP Publishing. - 2329-7778. ; 6:5
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Tidskriftsartikel (refereegranskat)abstract
- Phytochromes (PHYs) are photoreceptor proteins first discovered in plants, where they control a variety of photomorphogenesis events. PHYs as photochromic proteins can reversibly switch between two distinct states: a red light (Pr) and a far-red light (Pfr) absorbing form. The discovery of Bacteriophytochromes (BphPs) in nonphotosynthetic bacteria has opened new frontiers in our understanding of the mechanisms by which these natural photoswitches can control single cell development, although the role of BphPs in vivo remains largely unknown. BphPs are dimeric proteins that consist of a photosensory core module (PCM) and an enzymatic domain, often a histidine kinase. The PCM is composed of three domains (PAS, GAF, and PHY). It holds a covalently bound open-chain tetrapyrrole (biliverdin, BV) chromophore. Upon absorption of light, the double bond between BV rings C and D isomerizes and reversibly switches the protein between Pr and Pfr states. We report crystal structures of the wild-type and mutant (His275Thr) forms of the canonical BphP from the nonphotosynthetic myxobacterium Stigmatella aurantiaca (SaBphP2) in the Pr state. Structures were determined at 1.65A degrees and 2.2A degrees (respectively), the highest resolution of any PCM construct to date. We also report the room temperature wild-type structure of the same protein determined at 2.1A degrees at the SPring-8 Angstrom Compact free electron LAser (SACLA), Japan. Our results not only highlight and confirm important amino acids near the chromophore that play a role in Pr-Pfr photoconversion but also describe the signal transduction into the PHY domain which moves across tens of angstroms after the light stimulus. (C) 2019 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
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| 5. |
- af Geijerstam, Peder, 1983-, et al.
(författare)
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Potential organ donors after Out-of-Hospital Cardiac Arrest during a ten-year period in Stockholm, Sweden
- 2019
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Ingår i: Resuscitation. - Amsterdam, Netherlands : Elsevier. - 0300-9572 .- 1873-1570. ; 137, s. 215-220
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Tidskriftsartikel (refereegranskat)abstract
- Background:Donation after brain death (DBD) is current praxis in Sweden. Circulatory death is far more common. Donation from patients suffering Out-of-Hospital Cardiac Arrest (OHCA) may have the potential to increase the organ-donor pool. The aim of this study was to describe the potential donor pool and its characteristics if uncontrolled donation after circulatory death (uDCD) were to be implemented in the metropolitan area of Stockholm, Sweden.Methods:A retrospective analysis was made using data from the Swedish Register for cardiopulmonary resuscitation (SRCR) between 2006 and 2015. Evaluation of potential organ donors was made using selection criteria from five previously published protocols concerning uDCD.Results:When applying different criteria from each of the five studied protocols in a total of 9,793 cases of OHCA, between 7.5% (n = 732) and 1.5% (n = 150) of the patients were found to be potential candidates for uDCD. The median age of the sampled uDCD candidates in each protocol was between 48 and 57 years. Male donors were found in 67–76% of all cases.Conclusion:Although not taking important real-life limitations into account, our results indicate that implementation of a uDCD programme may substantially increase the number of potential organ donors in Stockholm.
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| 6. |
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| 7. |
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| 8. |
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| 9. |
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| 10. |
- Edlund, Petra, et al.
(författare)
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The room temperature crystal structure of a bacterial phytochrome determined by serial femtosecond crystallography
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Phytochromes are a family of photoreceptors that control light responses of plants, fungi and bacteria. A sequence of structural changes, which is not yet fully understood, leads to activation of an output domain. Time-resolved serial femtosecond crystallography (SFX) can potentially shine light on these conformational changes. Here we report the room temperature crystal structure of the chromophore-binding domains of the Deinococcus radiodurans phytochrome at 2.1 angstrom resolution. The structure was obtained by serial femtosecond X-ray crystallography from microcrystals at an X-ray free electron laser. We find overall good agreement compared to a crystal structure at 1.35 angstrom resolution derived from conventional crystallography at cryogenic temperatures, which we also report here. The thioether linkage between chromophore and protein is subject to positional ambiguity at the synchrotron, but is fully resolved with SFX. The study paves the way for time-resolved structural investigations of the phytochrome photocycle with time-resolved SFX.
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| 11. |
- Fredman, D., et al.
(författare)
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Experiences and outcome from the implementation of a national Swedish automated external defibrillator registry
- 2018
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 130, s. 73-80
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early cardiopulmonary resuscitation (CPR) and defibrillation with an Automated External Defibrillator (AED) increase survival from out-of-hospital cardiac arrest (OHCA). Although international guidelines recommend the use of AED registries to increase AED use, little is known about implementation. The aim of this paper is to describe the development of a national AED registry, to analyse the coverage and barriers to register AEDs. Methods: The Swedish AED Registry (SAEDREG) was initiated in 2009 with the purpose of gathering the data of all public AEDs in Sweden. Data on all AEDs between 2013 and 2016 were included in the study. Additionally, data of non-registered AEDs was collected in one region using a survey to AED owners focusing on AED functionality. Results: The number of AEDs doubled between 2013–2016. A total of 6703 AEDs (30%) were removed due to unavailability of validation. At the end of 2016, AEDs were most frequently registered in offices and workplaces, 45% (n = 7241) followed by shops, 7% (n = 1200). In the Gotland region, 218 AEDs, 57% (n = 124) were registered in the SAEDREG. Of n = 94 Non-registered AED functionality was high, the main reason not to register was unawareness of the SAEDREG, 74.5%. Of those aware of the register but not having registered, 25% stated “hard to register” as cause. Conclusions: A national AED registry may gather information of AEDs on a national level. Although numbers have doubled between 2013–2016 in Sweden, a large proportion is still non-registered. More awareness of the registry and easier registration process is needed. General AED functionality seems high regardless of registered or non-registered AEDs. A key area for future research may be to use AED-registers to ascertain effectiveness of AED programs in terms of actual patient outcome.
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| 12. |
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| 13. |
- Hollenberg, J, et al.
(författare)
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Effects of native language on CPR skills and willingness to intervene in out-of-hospital cardiac arrest after film-based basic life support training: a subgroup analysis of a randomised trial
- 2019
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 9:5, s. e025531-
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to investigate whether the students’ native language, Swedish as native language (SNL) versus other native language (ONL), affects cardiopulmonary resuscitation (CPR) skills or willingness to act after film-based training in Swedish.Setting13-year-old students in two municipalities.DesignA subgroup from a previous randomised study was analysed. During 2013 to 2014, a film-based CPR method was evaluated. Practical skills and willingness to act were assessed directly after training and after 6 months. CPR skills were evaluated using a modified Cardiff test.ParticipantsA total of 641 students were included in the analysis (SNL, n=499; ONL, n=142).Primary and secondary outcome measuresPrimary endpoint was the total score of the modified Cardiff test at 6 months. The secondary endpoints were total score directly after training, individual variables for the test and self-reported willingness to act.ResultsAt the practical test, SNL students scored better than ONL students; directly after training, 67% vs 61% of maximum score, respectively (p<0.001); at 6 months, 61% vs 56% of maximum score (p<0.001). Most students were willing to perform compressions and ventilation on a friend (SNL 85% vs ONL 84%). However, if the victim was a stranger, ONL students were more willing to perform both compressions and ventilation than SNL students (52% vs 38% after training, p<0.001; 42% vs 31% at 6 months, p=0.032). SNL students preferred to initiate chest compressions only.ConclusionsSNL students scored slightly higher in the practical CPR skill test than ONL students. Willingness to act was generally high, however ONL students reported higher willingness to perform both compressions and ventilation if the victim was a stranger. Further research is needed to investigate how CPR educational material should be designed and simplified for optimal learning by students. Different language versions or including feedback in CPR training can be a way to increase learning.Ethics approvalThe study was approved by the Regional Ethical Review Board of Linköping, Sweden (2013/358-31).Trial registration numberNCT03233490; Pre-results.
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| 14. |
- Niga, Petru, et al.
(författare)
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Interactions between model cell membranes and the neuroactive drug propofol
- 2018
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier BV. - 0021-9797 .- 1095-7103. ; 526, s. 230-243
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Tidskriftsartikel (refereegranskat)abstract
- phospholipid, NR data reveal that propofol is located exclusively in the head group region, which is rationalized in the context of previous studies. The results imply a non-homogeneous distribution of propofol in the plane of real cell membranes, which is an inference that requires urgent testing and may help to explain why such low concentration of the drug are required to induce general anaesthesia.
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| 15. |
- Niga, Petru, et al.
(författare)
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Propofol adsorption at the air/water interface : a combined vibrational sum frequency spectroscopy, nuclear magnetic resonance and neutron reflectometry study
- 2019
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Ingår i: Soft Matter. - : ROYAL SOC CHEMISTRY. - 1744-683X .- 1744-6848. ; 15:1, s. 38-46
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Tidskriftsartikel (refereegranskat)abstract
- Propofol is an amphiphilic small molecule that strongly influences the function of cell membranes, yet data regarding interfacial properties of propofol remain scarce. Here we consider propofol adsorption at the air/water interface as elucidated by means of vibrational sum frequency spectroscopy (VSFS), neutron reflectometry (NR), and surface tensiometry. VSFS data show that propofol adsorbed at the air/ water interface interacts with water strongly in terms of hydrogen bonding and weakly in the proximity of the hydrocarbon parts of the molecule. In the concentration range studied there is almost no change in the orientation adopted at the interface. Data from NR show that propofol forms a dense monolayer with a thickness of 8.4 angstrom and a limiting area per molecule of 40 angstrom(2), close to the value extracted from surface tensiometry. The possibility that islands or multilayers of propofol form at the air/water interface is therefore excluded as long as the solubility limit is not exceeded. Additionally, measurements of the 1H NMR chemical shifts demonstrate that propofol does not form dimers or multimers in bulk water up to the solubility limit.
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| 16. |
- Ringh, M, et al.
(författare)
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The challenges and possibilities of public access defibrillation.
- 2018
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 283:3, s. 238-256
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Tidskriftsartikel (refereegranskat)abstract
- Out-of-hospital cardiac arrest (OHCA) is a major health problem that affects approximately four hundred and thousand patients annually in the United States alone. It is a major challenge for the emergency medical system as decreased survival rates are directly proportional to the time delay from collapse to defibrillation. Historically, defibrillation has only been performed by physicians and in-hospital. With the development of automated external defibrillators (AEDs), rapid defibrillation by nonmedical professionals and subsequently by trained or untrained lay bystanders has become possible. Much hope has been put to the concept of Public Access Defibrillation with a massive dissemination of public available AEDs throughout most Western countries. Accordingly, current guidelines recommend that AEDs should be deployed in places with a high likelihood of OHCA. Despite these efforts, AED use is in most settings anecdotal with little effect on overall OHCA survival. The major reasons for low use of public AEDs are that most OHCAs take place outside high incidence sites of cardiac arrest and that most OHCAs take place in residential settings, currently defined as not suitable for Public Access Defibrillation. However, the use of new technology for identification and recruitment of lay bystanders and nearby AEDs to the scene of the cardiac arrest as well as new methods for strategic AED placement redefines and challenges the current concept and definitions of Public Access Defibrillation. Existing evidence of Public Access Defibrillation and knowledge gaps and future directions to improve outcomes for OHCA are discussed. In addition, a new definition of the different levels of Public Access Defibrillation is offered as well as new strategies for increasing AED use in the society.
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| 17. |
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| 18. |
- Sanfridsson, J, et al.
(författare)
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Drone delivery of an automated external defibrillator - a mixed method simulation study of bystander experience.
- 2019
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Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. - : Springer Science and Business Media LLC. - 1757-7241. ; 27:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Out-of-hospital cardiac arrest (OHCA) affects some 275,000 individuals in Europe each year. Time from collapse to defibrillation is essential for survival. As emergency medical services (EMS) response times in Sweden have increased, novel methods are needed to facilitate early treatment. Unmanned aerial vehicles (i.e. drones) have potential to deliver automated external defibrillators (AED). The aim of this simulation study was to explore bystanders' experience of a simulated OHCA-situation where a drone delivers an AED and how the situation is affected by having one or two bystanders onsite.METHODS: This explorative simulation study used a mixed methodology describing bystanders' experiences of retrieving an AED delivered by a drone in simulated OHCA situations. Totally eight participants were divided in two groups of bystanders a) alone or b) in pairs and performed CPR on a manikin for 5 minutes after which an AED was delivered by a drone at 50 m from the location. Qualitative data from observations, interviews of participants and video recordings were analysed using content analysis alongside descriptive data on time delays during bystander interaction.RESULTS: Three categories of bystander experiences emerged: 1) technique and preparedness, 2) support through conversation with the dispatcher, and 3) aid and decision-making. The main finding was that retrieval of an AED as delivered by a drone was experienced as safe and feasible for bystanders. None of the participants hesitated to retrieve the AED; instead they experienced it positive, helpful and felt relief upon AED-drone arrival and were able to retrieve and attach the AED to a manikin. Interacting with the AED-drone was perceived as less difficult than performing CPR or handling their own mobile phone during T-CPR. Single bystander simulation introduced a significant hands-off interval when retrieving the AED, a period lasting 94 s (range 75 s-110 s) with one participant compared to 0 s with two participants.CONCLUSION: The study shows that it made good sense for bystanders to interact with a drone in this simulated suspected OHCA. Bystanders experienced delivery of AED as safe and feasible. This has potential implications, and further studies on bystanders' experiences in real cases of OHCA in which a drone delivers an AED are therefore necessary.
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| 19. |
- Skelton, A., et al.
(författare)
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Hydrochemical Changes Before and After Earthquakes Based on Long-Term Measurements of Multiple Parameters at Two Sites in Northern IcelandA Review
- 2019
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Ingår i: Journal of Geophysical Research-Solid Earth. - : American Geophysical Union (AGU). - 2169-9313 .- 2169-9356. ; 124:3, s. 2702-2720
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Tidskriftsartikel (refereegranskat)abstract
- Hydrochemical changes before and after earthquakes have been reported for over 50years. However, few reports provide sufficient data for an association to be verified statistically. Also, no mechanism has been proposed to explain why hydrochemical changes are observed far from earthquake foci where associated strains are small (<10(-8)). Here we address these challenges based on time series of multiple hydrochemical parameters from two sites in northern Iceland. We report hydrochemical changes before and after M >5 earthquakes in 2002, 2012, and 2013. The longevity of the time series (10 and 16years) permits statistical verification of coupling between hydrochemical changes and earthquakes. We used a Student t test to find significant hydrochemical changes and a binomial test to confirm association with earthquakes. Probable association was confirmed for preseismic changes based on five parameters (Na, Si, K, O-18, and H-2) and postseismic changes based on eight parameters (Ca, Na, Si, Cl, F, SO4, O-18, and H-2). Using concentration ratios and stable isotope values, we showed that (1) gradual preseismic changes were caused by source mixing, which resulted in a shift from equilibrium and triggered water-rock interaction; (2) postseismic changes were caused by rapid source mixing; and (3) longer-term hydrochemical changes were caused by source mixing and mineral growth. Because hydrochemical changes occur at small earthquake-related strains, we attribute source mixing and water-rock interaction to microscale fracturing. Because fracture density and size scale inversely, we infer that mixing of nearby sources and water-rock interaction are feasible responses to small earthquake-related strains. Plain Language Summary Changes in groundwater chemistry before and after earthquakes have been reported for over 50years. However, few studies have been able to prove that the earthquakes caused these changes. Also, no study has explained why these changes are often reported far from where the earthquake occurred. Here we address these challenges based on measurements of groundwater chemistry made at two sites in northern Iceland over time periods of 10 and 16years. We used statistical methods to prove that the earthquakes caused changes of ground water chemistry both before and after the earthquakes. We showed that changes of groundwater chemistry before earthquakes were caused by slow mixing between different groundwaters, which triggered reactions with the wall rock that changed groundwater chemistry, and that changes of groundwater chemistry after earthquakes were causes by rapid mixing between different groundwaters. That these changes were detected far from where the earthquakes occurred suggests that cracking of the wall rock at a very small scale was all that was needed for mixing of different groundwaters and reactions with the wall rock to occur.
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| 20. |
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| 23. |
- A Monfared, Behzad, 1983-
(författare)
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Magnetic Refrigeration for Near Room-Temperature Applications
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Refrigeration plays a crucial role in many different sectors and consumes about 17% of the electricity produced globally. This significant energy consumption implies large share of refrigeration in primary energy consumption and other environmental impacts. In addition to the environmental impacts associated with energy consumption, the vapor-compression systems contribute in global warming due to the release of their gaseous refrigerants into the atmosphere. As an alternative technology for near room-temperature applications, magnetic refrigeration is proposed by some researchers to eliminate the release of gaseous refrigerants into the atmosphere and to reduce the energy consumption. This thesis is a compilation of a number of studies done on magnetic refrigeration for room-temperature applications.In the first study, the environmental impacts associated to magnetic refrigeration are looked at closely through a life cycle assessment. The life cycle assessment indicates that because of the environmental burdens related to the rare-earth materials used in magnetic refrigeration, the reduction in the environmental impacts is not guaranteed by switching to magnetic refrigeration technology. Accordingly to avoid the extra environmental impacts the magnetic refrigeration systems should use magnetic materials frugally, which requires an optimized design. In addition, operation with higher efficiency compared to vapor-compression systems is necessary to have environmental advantages, at least in some impact categories.A practical method to optimize the design of magnetic refrigeration systems, e.g. to have a compact design or high efficiency, is utilizing a flexible software model, with which the effect of varying different parameters on the performance of the system can be simulated. Such a software model of the magnetic refrigeration system is developed and validated in this project. In developing the model one goal is to add to the precision of the simulated results by taking more details into consideration. This goal is achieved by an innovative way of modeling the parasitic heat transfer and including the effect of the presence of magnetocaloric materials on the strength of the field created by the magnet assembly. In addition, some efforts are made to modify or correct the existing correlations to include the effect of binding agents used in some active magnetic regenerators. Validation of the developed software model is done using the experimental results obtained from the prototype existing at the Department of Energy Technology, KTH Royal Institute of Technology.One of the parameters that can be modified by the developed software model is the choice of the magnetocaloric materials for each layer in a layered active magnetic regenerator. Utilizing the software model for optimizing the choice of the materials for the layers reveals that materials with critical temperatures equal to the cyclic average temperature of the layers in which they are used do not necessarily result in the desired optimum performance. In addition, for maximizing different outputs of the models, such as energy efficiency or temperature lift sustained at the two ends of the regenerators, different choice of materials for the layers are needed. Therefore, in other studies seeking to improve one of the outputs of a system, the choice of the transition or critical temperatures of the materials for each layer is an additional parameter to be optimized.The prototype existing at the Department of Energy Technology, KTH Royal Institute of Technology, was initially designed for replacing the vapor-compression system of a professional refrigerator. However, it could not fulfil the requirements for which it was initially designed. The aforementioned developed simulation model is used to see how much the choice of the materials, size of the particles, and number of layers can enhance the performance while the operation frequency and flow rate of the heat transfer fluid are at their optimum values. In other words, in that study the room for improvement in the performance without applying major changes in the system such as the geometry of the regenerator, which implies redesigning the whole magnet assembly, is investigated. In the redesign process the effect of binding agent and the limitations associated to different properties of it is also investigated theoretically. Nevertheless, the study did not show that with keeping the geometry of the regenerators and the currently existing magnetocaloric materials the initial goals of the prototype can be achieved.In the next study more flexible choice of geometries and magnetocaloric materials are considered. In fact, in this study it is investigated how much the magnetocaloric materials need to be improved so that magnetic refrigeration systems can compete with vapor-compression ones in terms of performance. For the two investigated cases, the magnetic-field dependent properties of the currently existing materials are enough provided that some other issues such as low mechanical stability and inhomogeneity of the properties are solved. Nevertheless, for more demanding design criteria, such as delivering large cooling capacity over a considerable temperature span while the magnetic materials are used sparingly, the magnetic-field dependent properties need to be enhanced, as well.A less explored area in room-temperature magnetic refrigeration is the subject of another study included in the thesis. In this study, solid-state magnetic refrigeration systems with Peltier elements as heat switches are modeled. Since the Peltier elements consume electricity to pump heat, the modeled systems can be considered hybrid magnetocaloric-Peltier cooling systems. For such systems the detailed transient behavior of the Peltier elements together with layers of magnetocaloric materials are modeled. The mathematical model is suitable for implementation in programing languages without the need for commercial modeling platforms. The parameters affecting the performance of the modeled system are numerous, and optimization of them requires a separate study. However, the preliminary attempts on optimizing the modeled system does not give promising results. Accordingly, focusing on passive heat switches can be more beneficial.
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| 24. |
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| 25. |
- Caolo, Vincenza, et al.
(författare)
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Shear Stress and VE-Cadherin : The Molecular Mechanism of Vascular Fusion
- 2018
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - : LIPPINCOTT WILLIAMS & WILKINS. - 1079-5642 .- 1524-4636. ; 38:9, s. 2174-2183
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Vascular fusion represents an important mechanism of vessel enlargement during development; however, its significance in postnatal vessel enlargement is still unknown. During fusion, 2 adjoining vessels merge to share 1 larger lumen. The aim of this research was to identify the molecular mechanism responsible for vascular fusion.Approach and Results: We previously showed that both low shear stress and DAPT (N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester) treatment in the embryo result in a hyperfused vascular plexus and that increasing shear stress levels could prevent DAPT-induced fusion. We, therefore, investigated vascular endothelial-cadherin (VEC) phosphorylation because this is a common downstream target of low shear stress and DAPT treatment. VEC phosphorylation increases after DAPT treatment and decreased shear stress. The increased phosphorylation occurred independent of the cleavage of the Notch intracellular domain. Increasing shear stress rescues hyperfusion by DAPT treatment by causing the association of the phosphatase vascular endothelial-protein tyrosine phosphatase with VEC, counteracting VEC phosphorylation. Finally, Src (proto-oncogene tyrosine-protein kinase Src) inhibition prevents VEC phosphorylation in endothelial cells and can rescue hyperfusion induced by low shear stress and DAPT treatment. Moesin, a VEC target that was previously reported to mediate endothelial cell rearrangement during lumenization, relocalizes to cell membranes in vascular beds undergoing hyperfusion.Conclusions: This study provides the first evidence that VEC phosphorylation, induced by DAPT treatment and low shear stress, is involved in the process of fusion during vascular remodeling.
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| 26. |
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| 27. |
- Claesson, A, et al.
(författare)
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District nurses' perceptions of osteoporosis management: a qualitative study
- 2015
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Ingår i: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. - : Springer Science and Business Media LLC. - 1433-2965. ; 26:7, s. 1911-1918
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Tidskriftsartikel (refereegranskat)
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| 28. |
- Claesson, A., et al.
(författare)
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Unmanned aerial vehicles (drones) in out-of-hospital-cardiac-arrest
- 2016
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Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. - : BioMed Central (BMC). - 1757-7241. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The use of an automated external defibrillator (AED) prior to EMS arrival can increase 30-day survival in out-of-hospital cardiac arrest (OHCA) significantly. Drones or unmanned aerial vehicles (UAV) can fly with high velocity and potentially transport devices such as AEDs to the site of OHCAs. The aim of this explorative study was to investigate the feasibility of a drone system in decreasing response time and delivering an AED. Methods: Data of Global Positioning System (GPS) coordinates from historical OHCA in Stockholm County was used in a model using a Geographic Information System (GIS) to find suitable placements and visualize response times for the use of an AED equipped drone. Two different geographical models, urban and rural, were calculated using a multi-criteria evaluation (MCE) model. Test-flights with an AED were performed on these locations in rural areas. Results: In total, based on 3,165 retrospective OHCAs in Stockholm County between 2006-2013, twenty locations were identified for the potential placement of a drone. In a GIS-simulated model of urban OHCA, the drone arrived before EMS in 32 % of cases, and the mean amount of time saved was 1.5 min. In rural OHCA the drone arrived before EMS in 93 % of cases with a mean amount of time saved of 19 min. In these rural locations during (n = 13) test flights, latch-release of the AED from low altitude (3-4 m) or landing the drone on flat ground were the safest ways to deliver an AED to the bystander and were superior to parachute release. Discussion: The difference in response time for EMS between urban and rural areas is substantial, as is the possible amount of time saved using this UAV-system. However, yet another technical device needs to fit into the chain of survival. We know nothing of how productive or even counterproductive this system might be in clinical reality. Conclusions: To use drones in rural areas to deliver an AED in OHCA may be safe and feasible. Suitable placement of drone systems can be designed by using GIS models. The use of an AED equipped drone may have the potential to reduce time to defibrillation in OHCA.
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| 29. |
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| 30. |
- Claesson, J., et al.
(författare)
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Scandinavian clinical practice guideline on fluid and drug therapy in adults with acute respiratory distress syndrome
- 2016
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 60:6, s. 697-709
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Forskningsöversikt (refereegranskat)abstract
- Background: The objective of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI) task force on fluid and drug therapy in adults with acute respiratory distress syndrome (ARDS) was to provide clinically relevant, evidence-based treatment recommendations according to standards for trustworthy guidelines. Methods: The guideline was developed according to standards for trustworthy guidelines, including a systematic review of the literature and use of the GRADE methodology for assessment of the quality of evidence and for moving from evidence to recommendations. Results: A total of seven ARDS interventions were assessed. We suggest fluid restriction in patients with ARDS (weak recommendation, moderate quality evidence). Also, we suggest early use of neuromuscular blocking agents (NMBAs) in patients with severe ARDS (weak recommendation, moderate quality evidence). We recommend against the routine use of other drugs, including corticosteroids, beta2 agonists, statins, and inhaled nitric oxide (iNO) or prostanoids in adults with ARDS (strong recommendations: low-to high-quality evidence). These recommendations do not preclude the use of any drug or combination of drugs targeting underlying or co-existing disorders. Conclusion: This guideline emphasizes the paucity of evidence of benefit - and potential for harm - of common interventions in adults with ARDS and highlights the need for prudence when considering use of non-licensed interventions in this patient population.
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| 31. |
- Corada, Monica, et al.
(författare)
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Fine-Tuning of Sox17 and Canonical Wnt Coordinates the Permeability Properties of the Blood-Brain Barrier
- 2019
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Ingår i: Circulation Research. - 0009-7330 .- 1524-4571. ; 124:4, s. 511-525
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: The microvasculature of the central nervous system includes the blood-brain barrier (BBB), which regulates the permeability to nutrients and restricts the passage of toxic agents and inflammatory cells. Canonical Wnt/β-catenin signaling is responsible for the early phases of brain vascularization and BBB differentiation. However, this signal declines after birth, and other signaling pathways able to maintain barrier integrity at postnatal stage are still unknown.Objective: Sox17 (SRY [sex-determining region Y]-box 17) constitutes a major downstream target of Wnt/β-catenin in endothelial cells and regulates arterial differentiation. In the present article, we asked whether Sox17 may act downstream of Wnt/β-catenin in inducing BBB differentiation and maintenance.Methods and Results: Using reporter mice and nuclear staining of Sox17 and β-catenin, we report that although β-catenin signaling declines after birth, Sox17 activation increases and remains high in the adult. Endothelial-specific inactivation of Sox17 leads to increase of permeability of the brain microcirculation. The severity of this effect depends on the degree of BBB maturation: it is strong in the embryo and progressively declines after birth. In search of Sox17 mechanism of action, RNA sequencing analysis of gene expression of brain endothelial cells has identified members of the Wnt/β-catenin signaling pathway as downstream targets of Sox17. Consistently, we found that Sox17 is a positive inducer of Wnt/β-catenin signaling, and it acts in concert with this pathway to induce and maintain BBB properties. In vivo, inhibition of the β-catenin destruction complex or expression of a degradation-resistant β-catenin mutant, prevent the increase in permeability and retina vascular malformations observed in the absence of Sox17.Conclusions: Our data highlight a novel role for Sox17 in the induction and maintenance of the BBB, and they underline the strict reciprocal tuning of this transcription factor and Wnt/β-catenin pathway. Modulation of Sox17 activity may be relevant to control BBB permeability in pathological conditions.
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| 32. |
- Djarv, T., et al.
(författare)
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Traumatic cardiac arrest in Sweden 1990-2016 : a population-based national cohort study
- 2018
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Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. - : BioMed Central (BMC). - 1757-7241. ; 26
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Tidskriftsartikel (refereegranskat)abstract
- Background: Trauma is a main cause of death among young adults worldwide. Patients experiencing a traumatic cardiac arrest (TCA) certainly have a poor prognosis but population-based studies are sparse. Primarily to describe characteristics and 30-day survival following a TCA as compared with a medical out-of-hospital cardiac arrest (medical CA). Methods: A cohort study based on data from the nationwide, prospective population-based Swedish Registry for Cardiopulmonary Resuscitation (SRCR), a medical cardiac arrest registry, between 1990 and 2016. The definition of a TCA in the SRCR is a patient who is unresponsive with apnoea where cardiopulmonary resuscitation and/or defibrillation have been initiated and in whom the Emergency Medical Services (EMS, mainly a nurse-based system) reported trauma as the aetiology. Outcome was overall 30-day survival. Descriptive statistics as well as multivariable logistic regression models were used. Results: In all, between 1990 and 2016, 1774 (2.4%) cases had a TCA and 72,547 had a medical CA. Overall 30-day survival gradually increased over the years, and was 3.7% for TCAs compared to 8.2% following a medical CA (p < 0.01). Among TCAs, factors associated with a higher 30-day survival were bystander witnessed and having a shockable initial rhythm (adjusted OR 2.67, 95% C.I. 1.15-6.22 and OR 8.94 95% C.I. 4.27-18.69, respectively). Discussion: Association in registry-based studies do not imply causality but TCA had short time intervals in the chain of survival as well as high rates of bystander-CPR. C onclusion: In a medical CA registry like ours, prevalence of TCAs is low and survival is poor. Registries like ours might not capture the true incidence. However, many individuals do survive and resuscitation in TCAs should not be seen futile.
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| 33. |
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| 34. |
- Eriksson, Mimmi, et al.
(författare)
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Direct Observation of Gas Meniscus Formation on a Superhydrophobic Surface
- 2019
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Ingår i: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 13:2, s. 2246-2252
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Tidskriftsartikel (refereegranskat)abstract
- The formation of a bridging gas meniscus via cavitation or nanobubbles is considered the most likely origin of the submicrometer long-range attractive forces measured between hydrophobic surfaces in aqueous solution. However, the dynamics of the formation and evolution of the gas meniscus is still under debate, in particular, in the presence of a thin air layer on a superhydrophobic surface. On superhydrophobic surfaces the range can even exceed 10 μm. Here, we report microscopic images of the formation and growth of a gas meniscus during force measurements between a superhydrophobic surface and a hydrophobic microsphere immersed in water. This is achieved by combining laser scanning confocal microscopy and colloidal probe atomic force microscopy. The configuration allows determination of the volume and shape of the meniscus, together with direct calculation of the Young-Laplace capillary pressure. The long-range attractive interactions acting on separation are due to meniscus formation and volume growth as air is transported from the surface layer.
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| 35. |
- Eriksson, Mimmi, et al.
(författare)
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Wetting Transition on Liquid-Repellent Surfaces Probed by Surface Force Measurements and Confocal Imaging
- 2019
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Ingår i: Langmuir. - : AMER CHEMICAL SOC. - 0743-7463 .- 1520-5827. ; 35:41, s. 13275-13285
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Tidskriftsartikel (refereegranskat)abstract
- Superhydrophobic surfaces in the Cassie-Baxter wetting state retain an air layer at the surface which prevents liquid water from reaching into the porous surface structure. In this work we explore how addition of ethanol, which reduces the surface tension, influences the wetting properties of superhydrophobic and smooth hydrophobic surfaces. Wetting properties are measured by dynamic contact angles, and the air layer at the superhydrophobic surface is visualized by laser scanning confocal microscopy. Colloidal probe atomic force microscopy measurements between a hydrophobic microsphere and the macroscopic surfaces showed that the presence of ethanol strongly affects the interaction forces. When the macroscopic surface is superhydrophobic, attractive forces extending up to a few micrometers are observed on retraction in water and in 20 vol % ethanol, signifying the presence of a large and growing gas capillary. Submicrometer attractive forces are observed between the probe particle and a smooth hydrophobic surface, and in this case a smaller gas capillary is formed. Addition of ethanol results in markedly different effects between superhydrophobic and hydrophobic surfaces. In particular, we show that the receding contact angle on the superhydrophobic surface is of paramount importance for describing the interaction forces.
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| 36. |
- Fernandez-Alonso, R., et al.
(författare)
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p73 is required for endothelial cell differentiation, migration and the formation of vascular networks regulating VEGF and TGF beta signaling
- 2015
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Ingår i: Cell Death and Differentiation. - : Springer Science and Business Media LLC. - 1350-9047 .- 1476-5403. ; 22:8, s. 1287-
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Tidskriftsartikel (refereegranskat)abstract
- Vasculogenesis, the establishment of the vascular plexus and angiogenesis, branching of new vessels from the preexisting vasculature, involves coordinated endothelial differentiation, proliferation and migration. Disturbances in these coordinated processes may accompany diseases such as cancer. We hypothesized that the p53 family member p73, which regulates cell differentiation in several contexts, may be important in vascular development. We demonstrate that p73 deficiency perturbed vascular development in the mouse retina, decreasing vascular branching, density and stability. Furthermore, p73 deficiency could affect non endothelial cells (ECs) resulting in reduced in vivo proangiogenic milieu. Moreover, p73 functional inhibition, as well as p73 deficiency, hindered vessel sprouting, tubulogenesis and the assembly of vascular structures in mouse embryonic stem cell and induced pluripotent stem cell cultures. Therefore, p73 is necessary for EC biology and vasculogenesis and, in particular, that DNp73 regulates EC migration and tube formation capacity by regulation of expression of pro-angiogenic factors such as transforming growth factor-beta and vascular endothelial growth factors. DNp73 expression is upregulated in the tumor environment, resulting in enhanced angiogenic potential of B16-F10 melanoma cells. Our results demonstrate, by the first time, that differential p73-isoform regulation is necessary for physiological vasculogenesis and angiogenesis and DNp73 overexpression becomes a positive advantage for tumor progression due to its pro-angiogenic capacity.
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| 37. |
- Fredman, D., et al.
(författare)
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Expanding the first link in the chain of survival – Experiences from dispatcher referral of callers to AED locations
- 2016
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Ingår i: Resuscitation. - : Elsevier. - 0300-9572 .- 1873-1570. ; 107, s. 129-134
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Early use of automated external defibrillators (AED) increases survival in cases of out-of-hospital cardiac arrest (OHCA). Dispatchers play important roles in identifying OHCA, dispatching ambulances and providing callers with telephone-assisted cardiopulmonary resuscitation. Guidelines recommend that AED registries be linked to dispatch centres as tools to refer callers to nearby AED. Aim The aim of this study was to investigate to what extent dispatchers, when provided with a tool to display AED locations and accessibility, referred callers to nearby AED. Methods An application providing real-time visualization of AED locations and accessibility was implemented at four dispatch centres in Sweden. Dispatchers were instructed to refer callers to nearby AED when OHCA was suspected. Such cases were prospectively collected, and geographic information systems were used to identify those located ≤100 m from an AED. Audio recordings of emergency calls were assessed to evaluate the AED referral rate. Results Between February and August 2014, 3009 suspected OHCA calls were received. In 6.6% of those calls (200/3009), an AED was ≤100 m from the suspected OHCA. The AED was accessible and the caller was not alone on scene in 24% (47/200) of these cases. In two of those 47 cases (4.3%), the dispatcher referred the caller to the AED. Conclusion Despite a tool for dispatchers to refer callers to a nearby AED, referral was rare. Only a minority of the suspected OHCA cases occurred ≤100 m from an AED. We identified AED accessibility and callers being alone on scene as obstacles for AED referral.
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| 38. |
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| 39. |
- Ghaffarpour, N, et al.
(författare)
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Patients with lymphatic malformations who receive the immunostimulant OK-432 experience excellent long-term outcomes
- 2015
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 104:11, s. 1169-73
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Sclerotherapy is the primary treatment for lymphatic malformations. The aim of this study was to evaluate the long-term outcome in patients with lymphatic malformations treated with the immunostimulant OK-432 as a sclerosant.METHODS: Between 1998 and 2013, we enrolled 131 of 138 eligible patients treated with OK-432 for lymphatic malformations in a retrospective study. The malformations were categorised according to the International Society for the Study of Vascular Anomalies. The outcome was assessed with a clinical examination and a questionnaire.RESULTS: The lymphatic malformations were localised to the head/neck (60%), the trunk (20%) and the extremities (6%) or involved with more than one region (14%). Patients with microcystic (10%), macrocystic (21%) and mixed lymphatic malformations (69%) underwent a median number of three, two and two injection treatments, respectively. The median age at the first injection was 3.4 years. Good or excellent clinical outcomes were seen in 70% of the patients. The number of injections, previous treatment and lesion localisation, but not time to follow-up and cyst size, predicted the clinical outcome.CONCLUSION: OK-432 treatment resulted in a successful outcome in 70% of patients with lymphatic malformations. The long-term outcome was comparable to the short-term outcome.
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| 40. |
- Gustavsson, Ingvar, et al.
(författare)
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Lab sessions in VISIR laboratories
- 2016
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Ingår i: Proceedings of 2016 13th International Conference on Remote Engineering and Virtual Instrumentation, REV 2016. - : IEEE Press. ; , s. 350-352
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Konferensbidrag (refereegranskat)abstract
- Experimental activities with real components are an essential part of all courses including or devoted to electrical and electronic circuits theory and practice. The knowledge triangle composed of hand-written exercises, simulations and traditional lab experiments has been enriched with the possibility for students to conduct real experiments over the Internet, using remote labs. This tutorial is devoted to one such remote lab named Virtual Instrument Systems in Reality (VISIR). The Global Online Laboratory Consortium (GOLC) elected VISIR as the best remote controlled laboratory in the world, at the first time this distinction was awarded. At the end of this tutorial, attendees are expected to know what is VISIR, what can (not) be done with it, who is currently using it, and how can one integrate it in a given course curriculum.
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| 41. |
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| 42. |
- Kumpulainen, Risto A., et al.
(författare)
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Sweden to review its geological nomenclature
- 2017
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Ingår i: GFF. - : Informa UK Limited. - 1103-5897 .- 2000-0863. ; 139:1, s. 1-2
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Forskningsöversikt (refereegranskat)abstract
- All geoscientists working with the geology of Sweden are invited to join a common effort to review Swedish geological nomenclature and the naming of geological units and other features. A new guide, the Guide for geological nomenclature in Sweden, provides advice for this review process. The Geological Survey of Sweden will set up a new open and freely accessible database for geological names, and a dedicated name committee with mandate to formally approve proposed names will supervise the naming process. The success of this vital long-term commitment will depend on active participation of the geoscientific community at large.
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| 43. |
- Ljungstrom, L., et al.
(författare)
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Clinical evaluation of commercial nucleic acid amplification tests in patients with suspected sepsis
- 2015
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Ingår i: Bmc Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sepsis is a serious medical condition requiring timely administered, appropriate antibiotic therapy. Blood culture is regarded as the gold standard for aetiological diagnosis of sepsis, but it suffers from low sensitivity and long turnaround time. Thus, nucleic acid amplification tests (NAATs) have emerged to shorten the time to identification of causative microbes. The aim of the present study was to evaluate the clinical utility in everyday practice in the emergency department of two commercial NAATs in patients suspected with sepsis. Methods: During a six-week period, blood samples were collected consecutively from all adult patients admitted to the general emergency department for suspicion of a community-onset sepsis and treated with intravenous antibiotics. Along with conventional blood cultures, multiplex PCR (Magicplex (TM)) was performed on whole blood specimens whereas portions from blood culture bottles were used for analysis by microarray-based assay (Prove-it (TM)). The aetiological significance of identified organisms was determined by two infectious disease physicians based on clinical presentation and expected pathogenicity. Results: Among 382 episodes of suspected sepsis, clinically relevant microbes were detected by blood culture in 42 episodes (11%), by multiplex PCR in 37 episodes (9.7%), and by microarray in 32 episodes (8.4%). Although moderate agreement with blood culture (kappa 0.50), the multiplex PCR added diagnostic value by timely detection of 15 clinically relevant findings in blood culture-negative specimens. Results of the microarray corresponded very well to those of blood culture (kappa 0.90), but were available just marginally prior to blood culture results. Conclusions: The use of NAATs on whole blood specimens in adjunct to current culture-based methods provides a clinical add-on value by allowing for detection of organisms missed by blood culture. However, the aetiological significance of findings detected by NAATs should be interpreted with caution as the high analytical sensitivity may add findings that do not necessarily corroborate with the clinical diagnosis.
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| 44. |
- Llona-Minguez, Sabin, et al.
(författare)
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Discovery of the First Potent and Selective Inhibitors of Human dCTP Pyrophosphatase 1
- 2016
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 59:3, s. 1140-1148
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Tidskriftsartikel (refereegranskat)abstract
- The dCTPase pyrophosphatase 1 (dCTPase) regulates the intracellular nucleotide pool through hydrolytic degradation of canonical and noncanonical nucleotide triphosphates (dNTPs). dCTPase is highly expressed in multiple carcinomas and is associated with cancer cell sternness. Here we report on the development of the first potent and selective dCTPase inhibitors that enhance the cytotoxic effect of cytidine analogues in leukemia cells. Boronate 30 displays a promising in vitro ADME profile, including plasma and mouse microsomal half-lives, aqueous solubility, cell permeability and CYP inhibition, deeming it a suitable compound for in vivo studies.
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| 45. |
- Palkopoulou, Eleftheria, et al.
(författare)
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A comprehensive genomic history of extinct and living elephants
- 2018
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : NATL ACAD SCIENCES. - 0027-8424 .- 1091-6490. ; 115:11, s. E2566-E2574
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Tidskriftsartikel (refereegranskat)abstract
- Elephantids are the world's most iconic megafaunal family, yet there is no comprehensive genomic assessment of their relationships. We report a total of 14 genomes, including 2 from the American mastodon, which is an extinct elephantid relative, and 12 spanning all three extant and three extinct elephantid species including an similar to 120,000-y-old straight-tusked elephant, a Columbian mammoth, and woolly mammoths. Earlier genetic studies modeled elephantid evolution via simple bifurcating trees, but here we show that interspecies hybridization has been a recurrent feature of elephantid evolution. We found that the genetic makeup of the straight-tusked elephant, previously placed as a sister group to African forest elephants based on lower coverage data, in fact comprises three major components. Most of the straight-tusked elephant's ancestry derives from a lineage related to the ancestor of African elephants while its remaining ancestry consists of a large contribution from a lineage related to forest elephants and another related to mammoths. Columbian and woolly mammoths also showed evidence of interbreeding, likely following a latitudinal cline across North America. While hybridization events have shaped elephantid history in profound ways, isolation also appears to have played an important role. Our data reveal nearly complete isolation between the ancestors of the African forest and savanna elephants for similar to 500,000 y, providing compelling justification for the conservation of forest and savanna elephants as separate species.
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| 46. |
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| 47. |
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| 48. |
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